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Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis

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ABSTRACT

Objectives

To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis.

Methods

Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40–85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection.

Results

Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with Tmax 3 times shorter and apparent T1/2 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40 µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection.

Conclusions

These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.

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REFERENCES

  1. Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang DD, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release. 2004;97:503–11.

    CAS  PubMed  Google Scholar 

  2. Matriano JA, Cormier M, Johnson J, Young WA, Buttery M, Nyam K, et al. Macroflux® microprojection array patch technology: a new and efficient approach for intracutaneous immunization. Pharm Res. 2002;19:63–70.

    Article  CAS  PubMed  Google Scholar 

  3. Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE, et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine. 2006;24:1653–64.

    Article  CAS  PubMed  Google Scholar 

  4. Daddona PE. Macroflux® transdermal technology development for the delivery of therapeutic peptides and proteins. Drug Delivery Technology. 2002;2:54–7.

    CAS  Google Scholar 

  5. Sathyan G, Sun Y-N, Weyers R, Daddona P, Staehr P, Gupta S. Macroflux® desmopressin transdermal delivery system: pharmacokinetics and pharmacodynamic evaluation in healthy volunteers. AAPS J. 2004;6(S1):665.

    Google Scholar 

  6. Ameri M, Peters EE, Wang X, Daddona PE, Y-F Maa. Erythropoietin (EPO) coated microprojection transdermal system: pre-clinical formulation, stability and delivery. AAPS J. 2009;11(S2):T2245.

    Google Scholar 

  7. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–41.

    Article  CAS  PubMed  Google Scholar 

  8. Cosman F. Parathyroid hormone treatment of osteoporosis. Curr Opin Endocrinol Diab Obes. 2008;15:495–501.

    CAS  Google Scholar 

  9. Fraenkel L, Gulanski B, Wittink D. Patient treatment preferences for osteoporosis. Arthritis Rheum. 2006;5:729–35.

    Article  Google Scholar 

  10. Fraenkel L, Gulanski B, Wittink D. Patient willingness to take teriparatide. Patient Educ Couns. 2007;65(2):237–44.

    Article  PubMed  Google Scholar 

  11. Fraher LJ, Avram R, Watson PH, Hendy GN, Henderson JE, Chong KL, et al. Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in health humans. J Clin Endocrinol Metab. 1999;8:2739–43.

    Article  Google Scholar 

  12. Frolik CA, Black EC, Cain RL, Satterwhite JH, Brown-Aµgsburger PL, Sato M, et al. Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure. Bone. 2003;33:372–9.

    Article  CAS  PubMed  Google Scholar 

  13. Kitazawa R, Imai Y, Fukase M, Fujita T. Effects of continuous infusion of parathyroid hormone-related peptide on rat bone in vivo: comparative study by histomorphometry. Bone Miner. 1991;12:157–66.

    Article  CAS  PubMed  Google Scholar 

  14. Hock JM, Gera I. Effects of continuous and intermittent administration and inhibition of resorption of the anabolic response of bone to parathyroid hormone. J Bone Miner Res. 1992;7:65–72.

    Article  CAS  PubMed  Google Scholar 

  15. Potter LK, Greller LD, Cho CR, Nuttall ME, Stroup GB, Suva LJ, et al. Response to continuous and pulsatile PTH dosing: a mathematical model for parathyroid hormone receptor kinetics. Bone. 2005;37:159–69.

    Article  CAS  PubMed  Google Scholar 

  16. Komarova SV. Mathematical model of paracrine interactions between osteoclasts and osteoblasts predicts anabolic action of parathyroid hormone on bone. Endocrinol. 2005;146:3589–95.

    Article  CAS  Google Scholar 

  17. Gopalakrishnan V, Hwang S, Loughrey H, Alexandre B, Desai D, Haiying L, et al. Administration of ThPTH to humans using Macroflux transdermal technology results in the rapid delivery of biological active PTH. J Bone Miner Res. 2004;19 Suppl 1:S460.

    Google Scholar 

  18. Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, et al. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2010;95:151–8.

    Article  CAS  PubMed  Google Scholar 

  19. Cormier M, Neukermans AP, Block B, Theeuwes FT, Amkraut A. A device for enhancing transdermal agent delivery or sampling. EP0914178B1, 2003.

  20. Ameri M, Daddona PE, Maa Y-F. Demonstrated solid-state stability of parathyroid hormone PTH (1-34) coated on a novel transdermal microprojection delivery system. Pharm Res. 2009;26:2454–63.

    Article  CAS  PubMed  Google Scholar 

  21. Ameri M, Maa Y-F. Parathyroid hormone PTH (1-34) formulation that enables uniform coating on a novel transdermal microprojection delivery system. Pharm Res. 2009;27:303–13.

    Article  PubMed  Google Scholar 

  22. Trautman JC, Wright CT, Cormier M. Method and apparatus for coating skin piercing microneedles. US Patent 6,855,372, 2002.

  23. Trautman JC, Keenan RL, Samiee AP, Lin W-Q, Cormier M, Matriano JA, et al. Apparatus and method for piercing skin with microprotrusion. US Patent 7,131,960, 2008.

  24. Chen K, Nguyen H, Zhu J, Shi Y, Prince P, Scott G, et al. Development and validation of a specific/sensitive/robust ELISA for quantification of human PTH (1-34) in human plasma: issues, possible solutions. AAPS J. 2006;8 Suppl 2:1995.

    Google Scholar 

  25. McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005;165:1762–8.

    Article  CAS  PubMed  Google Scholar 

  26. Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S, et al. Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res. 2008;23:1591–600.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGEMENTS

The authors would like to thank Mary Southam, Asha Ramdas, Stephen Hwang, Michel Cormier and Creag Trautman for their valuable insights and contributions to this product development over the past several years.

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Authors and Affiliations

  1. Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California, 94555, USA

    Peter E. Daddona, James. A. Matriano & Yuh-Fun Maa

  2. Quantitative Solutions, Inc., 845 Oak Grove Avenue, Suite 100, Menlo Park, California, 94025, USA

    Jaap Mandema

Authors
  1. Peter E. Daddona
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  2. James. A. Matriano
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  3. Jaap Mandema
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  4. Yuh-Fun Maa
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Corresponding author

Correspondence to Peter E. Daddona.

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Daddona, P.E., Matriano, J.A., Mandema, J. et al. Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis. Pharm Res 28, 159–165 (2011). https://doi.org/10.1007/s11095-010-0192-9

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  • DOI: https://doi.org/10.1007/s11095-010-0192-9

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